Programmed death-1 (PD-1) and Programmed death-1 ligand (PD-L1) regulate immune response. Previous studies associate an immune deregulation in ST-elevation myocardial infarction STEMI.
We recruited 100 patients with a first STEMI treated with reperfusion. In all patients PD-1 and PD-L1 expression was studied 24 h post-reperfusion in peripheral blood mononuclear cells (PBMCs), by means of flow cytometry and molecular biology. PD-1 and PD-L1 expression was serially analyzed in the first 20 patients before reperfusion and 24h, 96h and 30 days afterwards. Results were compared with 30 age- and sex-matched controls. Cardiac Magnetic Resonance was used to quantify infarct size 1-week after infarction. In a series of 8 swine with induced STEMI, PD-1 and PD-L1 expression was analyzed at baseline, 90 min after balloon inflation, 2 h and 24 h after reperfusion in PBMCs, and in swine hearts. Results were compared to 5 controls.
In patients, in comparison with controls, a significant decrease of PD-1 expression [mRNA fold change 0.8 ± 0.3 vs. 1.2 ± 0.6] and an increase of PD-L1+ expression [mRNA fold change 2.7 ± 2.1 vs. 0.9 ± 0.5] was observed 24h after infarction in PBMCs (p <0.05). STEMI patients with large infarct size showed decreased PD-1 expression, PD-L1 did not changed (Figure 1). Both in patients and swine, showed a significant increase of PD-1 and PD-L1 expression before reperfusion. Swine hearts revealed a marked infiltration of PMBCs and a significant increase of PD-1 and PD-L1 expression in the infarcted area compared to controls (Figure 2)
Acute changes in the PD-1 pathway take place in acute STEMI. A lesser expresion of PD-1 in peripheral blood, which could be due to myocardial infiltration in the infarcted area of PBMCs, associates with a larger infarct size.